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| Fetal anomalies v1.73 | MED11 |
Ain Roesley gene: MED11 was added gene: MED11 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: MED11 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MED11 were set to 36001086 Phenotypes for gene: MED11 were set to neurodevelopmental disorder MONDO#0700092, MED11-related Review for gene: MED11 was set to AMBER gene: MED11 was marked as current diagnostic Added comment: 7 affected from 5 families (3x consang) with the same recurrent variant of p.(Arg109*). Protein truncating, NOT NMD as proven by RT-PCR and western blot. Zebrafish knockout model recapitulates key clinical phenotypes NO evidence of founder effect from haplotype analysis 7/7 cerebral dysgyria, cortical atrophy 5/7 limb contracture 4/7 epilepsy 3/7 families with IUGR 3/7 GDD 3/7 hearing loss 3/7 undescended testis 2/7 nystagmus 1/7 congenital cataract Sources: Literature |
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| Fetal anomalies v1.3 | IRX5 | Zornitza Stark edited their review of gene: IRX5: Added comment: Third family with Hamamy syndrome and homozygous missense variant reported, p.Arg168His. Two cousins, >4 meioses, good segregation data.; Changed rating: GREEN; Changed publications: 22581230, 27453922, 34899143 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3697 | HECW2 |
Zornitza Stark changed review comment from: Typically denovo missense variants in the HECT domain. PMID: 29807643 - R1191Q single case with severe D/ID, EE and regression PMID: 29395664 - single case with regression, loss of swallowing, increased abnormal movements/hand stereotypies, Rett like, cortical visual impairment and EE PMID: 27334371 - propose GOF or dominant negative; 1 case plus references 5 previous cases PMID: 27389779 - four novel de novo predicted deleterious missense variants in HECW2 in six probands with ID/developmental delay and hypotonia. Other common features include seizures, strabismus, nystagmus, cortical visual impairment and dysmorphic facial features. p. Arg1330Trp, p.Glu1445Gly reported >1 case. Regression reported in the context of refractory EE; to: Clinical presentation is typically post-natal. Typically denovo missense variants in the HECT domain. PMID: 29807643 - R1191Q single case with severe D/ID, EE and regression PMID: 29395664 - single case with regression, loss of swallowing, increased abnormal movements/hand stereotypies, Rett like, cortical visual impairment and EE PMID: 27334371 - propose GOF or dominant negative; 1 case plus references 5 previous cases PMID: 27389779 - four novel de novo predicted deleterious missense variants in HECW2 in six probands with ID/developmental delay and hypotonia. Other common features include seizures, strabismus, nystagmus, cortical visual impairment and dysmorphic facial features. p. Arg1330Trp, p.Glu1445Gly reported >1 case. Regression reported in the context of refractory EE |
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| Fetal anomalies v0.1629 | ARG1 | Zornitza Stark Marked gene: ARG1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1629 | ARG1 | Zornitza Stark Gene: arg1 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1629 | ARG1 | Zornitza Stark Phenotypes for gene: ARG1 were changed from ARGININEMIA to Argininaemia, MIM# 207800 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1628 | ARG1 | Zornitza Stark reviewed gene: ARG1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Argininaemia, MIM# 207800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.957 | DNAH1 |
Krithika Murali gene: DNAH1 was added gene: DNAH1 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: DNAH1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DNAH1 were set to 25927852; 31507630 Phenotypes for gene: DNAH1 were set to Situs inversus; primary ciliary dyskinesia; infertility Review for gene: DNAH1 was set to AMBER Added comment: PMID - 25927852 x2 siblings from consanguineous Saudi family with homozygous missense variants (p.Lys1154Gln). More detailed clinical information available for proband diagnosed with Kartagener syndrome - chronic respiratory infections, situs inversus and infertility. Sister also reported to have been diagnosed with Kartagener syndrome at a similar age but no additional clinical information provided. PMID: 31765523 - 1 patient with PCD with a single het missense. PMID: 24360805 - 7 patients (4 different variants) with homozygous variants and infertility due to defective sperm. Microscopy of sperm revealed dynein disorganization PMID: 31507630 - 1 chet patient with kartagener syndrome, a subtype of PCD. Variants were classified as VUS initially - now c.442C>T (p.Arg148Cys) remains VUS, c.3103C > T p.R1035C re-classified as likely benign. Additional patient was het for a single nonsense, authors acknowledge missed 2nd hit and that this alone was not causative. Currently listed as red gene in Heterotaxy panel Sources: Literature |
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| Fetal anomalies v0.921 | POLR1B |
Zornitza Stark gene: POLR1B was added gene: POLR1B was added to Fetal anomalies. Sources: Expert Review Mode of inheritance for gene: POLR1B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: POLR1B were set to 31649276 Phenotypes for gene: POLR1B were set to Treacher-Collins syndrome type 4 Review for gene: POLR1B was set to GREEN Added comment: Five unrelated families and a zebrafish model, variant inherited in two of the families, once from affected parent and once from mosaic parent. Note four of the families had missense variants affecting same residue, p.Arg1003 Sources: Expert Review |
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| Fetal anomalies v0.158 | ADCY6 |
Krithika Murali gene: ADCY6 was added gene: ADCY6 was added to Fetal anomalies. Sources: Expert list,Literature Mode of inheritance for gene: ADCY6 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ADCY6 were set to 24319099, 26257172, 31846058; 33820833 Phenotypes for gene: ADCY6 were set to Lethal congenital contracture syndrome 8 - #616287 Review for gene: ADCY6 was set to GREEN Added comment: PMID: 33820833 (2021) - Further 2 sibs reported with a homozygous c.3346C>T:p.Arg1116Cys variant in the ADCY6 gene. The family was identified from a cohort of 315 genetically undiagnosed and unrelated AMC families. Arthrogryposis and IUGR were detected prenatally. Laquerriere et al. (2014): 2 sibs from a consanguineous family with an axoglial form of lethal congenital contracture syndrome, and homozygous missense ADCY6 mutation (R1116C). The parents were heterozygous for the mutation. Knocked down ADCY6 orthologs in zebrafish showed a loss of myelin basic protein expression in the peripheral nervous system but no defects in Schwann cell migration and axonal growth. Gonzaga‐Jauregui et al. (2015): 1 patient with congenital hypotonia, distal joint contractures, hypomyelinating neuropathy, and vocal cord paralysis, and a homozygous missense ADCY6 variant. No functional studies. Deceased sister with a similar phenotype with hypotonia, areflexia, and hypomyelinating neuropathy who died at 18 months of respiratory insufficiency. Agolini et al. (2020): 1 patient with severe form of AMC, with two novel compound heterozygous variants in ADCY6 (parents confirmed carriers), but no functional studies. Sources: Expert list, Literature |
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| Fetal anomalies v0.22 | ACTA2 |
Krithika Murali edited their review of gene: ACTA2: Added comment: Multisystemic smooth muscle dysfunction syndrome (MSMDS) presents with a recognizable pattern of complications, including congenital mydriasis, patent ductus arteriosus (PDA), pulmonary artery hypertension, aortic and other arterial aneurysms, moyamoya-like cerebrovascular disease, intestinal hypoperistalsis and malrotation, and hypotonic bladder. More than 40 unrelated individuals reported, missense at p.Arg179 position.; Changed rating: GREEN; Changed publications: 20734336, 29300374; Changed phenotypes: Multisystemic smooth muscle dysfunction syndrome - MIM# 613834 |
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| Fetal anomalies v0.0 | ARG1 |
Zornitza Stark gene: ARG1 was added gene: ARG1 was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp Mode of inheritance for gene: ARG1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: ARG1 were set to ARGININEMIA |
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